NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
Department of Human Biology and Human Movement Sciences, Maastricht University Medical Center, Maastricht, The Netherlands.
Clin Sci (Lond). 2017 Jul 7;131(15):1905-1917. doi: 10.1042/CS20170261. Print 2017 Aug 1.
Non-alcoholic fatty liver (NAFL) is an independent risk factor for the development of type 2 diabetes (T2DM). We examined metabolic perturbations in patients with NAFL, patients with T2DM, and control (CON) subjects with normal intrahepatic lipid (IHL) content.A two-step (10 mU/m /min; 40 mU/m/min) hyperinsulinemic-euglycemic clamp was performed in 11 NAFL, 13 T2DM, and 11 CON subjects, all matched for BMI, and aerobic fitness. IHL content was measured using proton magnetic resonance spectroscopy. Because of high IHL content variability in T2DM patients, this group was separated into a high IHL content group (IHL ≥ 5.0%, T2DM+NAFL) and a normal IHL content group (IHL < 5.0%, T2DM-non-NAFL) for further analysis.IHL content was increased in NAFL and T2DM+NAFL subjects (<0.050 versus CON and T2DM-non-NAFL subjects). Adipose tissue insulin sensitivity index (Adipo-IR) was higher in NAFL (<0.050 versus CON and T2DM-non-NAFL subjects) and in T2DM+NAFL subjects (=0.055 versus CON subjects, <0.050 versus T2DM-non-NAFL subjects). Suppression of plasma-free fatty acids (=0.046) was lower in NAFL compared with CON subjects, with intermediate values for T2DM-non-NAFL, and T2DM+NAFL subjects. Suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disposal (Δ) was comparable between NAFL, T2DM-non-NAFL, and T2DM+NAFL subjects (all >0.05), and was lower in comparison with CON subjects (all <0.01). Metabolic flexibility was lower in T2DM-non-NAFL subjects (=0.047) and NAFL subjects (=0.059) compared with CON subjects. Adipo-IR (=0.652, <0.001), hepatic insulin resistance index (HIR) (=0.576, =0.001), and Δ (=-0.653, <0.001) correlated with IHL content.Individuals with NAFL suffer from metabolic perturbations to a similar degree as T2DM patients. NAFL is an important feature leading to severe insulin resistance and should be viewed as a serious health threat for the development of T2DM. ClinicalTrials.gov: NCT01317576.
非酒精性脂肪肝 (NAFL) 是 2 型糖尿病 (T2DM) 发展的独立危险因素。我们检查了具有正常肝内脂质 (IHL) 含量的 NAFL 患者、T2DM 患者和对照 (CON) 受试者的代谢紊乱。在 11 名 NAFL、13 名 T2DM 和 11 名 CON 受试者中进行了两步（10 mU/m /min；40 mU/m/min）高胰岛素-正常血糖钳夹，所有受试者均按 BMI 和有氧健身匹配。使用质子磁共振波谱法测量 IHL 含量。由于 T2DM 患者的 IHL 含量变化较大，该组分为 IHL 含量高的组（IHL≥5.0%，T2DM+NAFL）和 IHL 含量正常的组（IHL<5.0%，T2DM-非-NAFL）进行进一步分析。IHL 含量在 NAFL 和 T2DM+NAFL 受试者中增加（<0.050 与 CON 和 T2DM-非-NAFL 受试者相比）。NAFL 受试者的脂肪组织胰岛素敏感性指数（Adipo-IR）较高（<0.050 与 CON 和 T2DM-非-NAFL 受试者相比），T2DM+NAFL 受试者的 Adipo-IR 较高（=0.055 与 CON 受试者相比，<0.050 与 T2DM-非-NAFL 受试者相比）。与 CON 受试者相比，NAFL 受试者的血浆游离脂肪酸抑制率（=0.046）较低，而 T2DM-非-NAFL 和 T2DM+NAFL 受试者的抑制率则处于中间水平。内源性葡萄糖生成（EGP）和胰岛素刺激的葡萄糖摄取（Δ）的抑制在 NAFL、T2DM-非-NAFL 和 T2DM+NAFL 受试者之间相似（均>0.05），与 CON 受试者相比均较低（均<0.01）。T2DM-非-NAFL 受试者（=0.047）和 NAFL 受试者（=0.059）的代谢灵活性低于 CON 受试者。Adipo-IR（=0.652，<0.001）、肝胰岛素抵抗指数（HIR）（=0.576，=0.001）和 Δ（=-0.653，<0.001）与 IHL 含量相关。NAFL 患者的代谢紊乱程度与 T2DM 患者相似。NAFL 是导致严重胰岛素抵抗的重要特征，应被视为发展为 T2DM 的严重健康威胁。ClinicalTrials.gov：NCT01317576。
